Variant chr7-21705443-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001277115.2(DNAH11):c.6469-17A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,612,334 control chromosomes in the GnomAD database, including 86,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 19566 hom., cov: 33)

Exomes 𝑓: 0.26 ( 66900 hom. )

Consequence

DNAH11
NM_001277115.2 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.349

Variant links:

Genes affected

DNAH11 (HGNC:2942): (dynein axonemal heavy chain 11) This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility. [provided by RefSeq, Mar 2013]

DNAH11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 7-21705443-A-G is Benign according to our data. Variant chr7-21705443-A-G is described in ClinVar as [Benign]. Clinvar id is 257920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21705443-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.6469-17A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.6469-17A>G		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001277115.2	ENSP00000475939	P1

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65257

AN:

152010

Hom.:

19511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.814

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.742

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.365

GnomAD3 exomes

AF:

0.366

AC:

90798

AN:

247876

Hom.:

22137

AF XY:

0.350

AC XY:

47042

AN XY:

134404

show subpopulations

Gnomad AFR exome

AF:

0.832

Gnomad AMR exome

AF:

0.536

Gnomad ASJ exome

AF:

0.195

Gnomad EAS exome

AF:

0.744

Gnomad SAS exome

AF:

0.435

Gnomad FIN exome

AF:

0.297

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.292

GnomAD4 exome

AF:

0.262

AC:

382811

AN:

1460206

Hom.:

66900

Cov.:

AF XY:

0.264

AC XY:

191512

AN XY:

726344

show subpopulations

Gnomad4 AFR exome

AF:

0.841

Gnomad4 AMR exome

AF:

0.524

Gnomad4 ASJ exome

AF:

0.196

Gnomad4 EAS exome

AF:

0.767

Gnomad4 SAS exome

AF:

0.431

Gnomad4 FIN exome

AF:

0.290

Gnomad4 NFE exome

AF:

0.201

Gnomad4 OTH exome

AF:

0.304

GnomAD4 genome

AF:

0.430

AC:

65382

AN:

152128

Hom.:

19566

Cov.:

AF XY:

0.437

AC XY:

32487

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.814

Gnomad4 AMR

AF:

0.443

Gnomad4 ASJ

AF:

0.201

Gnomad4 EAS

AF:

0.742

Gnomad4 SAS

AF:

0.456

Gnomad4 FIN

AF:

0.295

Gnomad4 NFE

AF:

0.205

Gnomad4 OTH

AF:

0.368

Alfa

AF:

0.261

Hom.:

7478

Bravo

AF:

0.456

Asia WGS

AF:

0.609

AC:

2115

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Primary ciliary dyskinesia 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.47

DANN

Benign

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over